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Neuronavigation-guided FUS-induced BBB Opening in Alzheimer's Disease Patients and Its Effects on Brain Amyloid and Tau

Neuronavigation-guided Focused Ultrasound-induced Blood-brain Barrier Opening in Alzheimer's Disease Patients and Its Effects on Brain Amyloid and Tau

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
50 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Ultrasound

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "The primary purpose of this phase 1b study is to further assess the safety and reversibility of focused ultrasound induced blood-brain barrier opening (FUS-BBBO) in participants with Alzheimer´s Disease (AD) using a single-element transducer with neuronavigation guidance."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests whether focused sound waves can safely open the brain’s protective barrier and let it close again. It also uses PET scans to check whether this lowers amyloid and tau, proteins that build up in Alzheimer’s disease. It is for adults over 50 with Alzheimer’s disease or mild cognitive impairment, which causes memory or thinking problems.

The primary purpose of this phase 1b study is to further assess the safety and reversibility of focused ultrasound induced blood-brain barrier opening (FUS-BBBO) in participants with Alzheimer´s Disease (AD) using a single-element transducer with neuronavigation guidance. Preliminary results from our phase 1a study demonstrate that our neuronavigation-guided FUS system was capable of safely and transiently open the BBB in participants with AD. The information collected in this new study may be used to design future clinical trials to ultimately provide a viable alternative for treatment of AD in a safe and noninvasive manner. Our secondary objective includes the assessment of the therapeutic efficacy of FUS-BBBO in reducing amyloid beta and neurofibrillary tangles, the main hallmark pathologies of AD, using PET tracers. Based on our preclinical studies in AD transgenic mouse models, FUS-BBBO alone was able to reduce both the amyloid beta and tau protein load, resulting in improvements in behavioral tasks assessing memory. Therefore, in this new study, the effect of FUS-BBBO on the amyloid beta and tau protein load in patients with AD will be assessed through the use of PET tracers.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be older than 50.
  • Have mild cognitive impairment or Alzheimer’s disease.
  • Have an MMSE memory and thinking test score of 12 to 26.
  • Have a Modified Hachinski Ischemia Scale score of 4 or less, which checks for signs of blood flow problems in the brain.
  • Have a short-form Geriatric Depression Scale score of 6 or less.
  • Have an Amyvid PET scan showing amyloid protein buildup in the brain.
  • Have an MK-6240 PET scan showing tau protein buildup in the front part of the brain.
  • Be able to understand the study and agree to take part.

Who can't join

  • Have ever received a drug that lowers amyloid, such as aducanumab or lecanemab.
  • Cannot safely have an MRI; have metal implants; or cannot receive MRI contrast dye or microbubbles, including because of a PEG allergy.
  • Have had brain surgery, including deep brain stimulation, or have a history of seizures.
  • Have abnormal blood-clotting tests or platelet levels, or take blood thinners that prevent clotting.
  • Have brain shrinkage that blocks ultrasound delivery; more than 4 tiny bleeds in the brain’s lobes; iron deposits from bleeding; larger brain bleeds; or a significant brain tumor or other growth.
  • Can become pregnant or are breastfeeding.
  • Have severely reduced kidney function (eGFR below 30), an active infection or inflammation, or an uncontrolled health problem that could make the study unsafe.
  • Cannot follow the study steps, including follow-up scans.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria. AD patients will be recruited in person and have to be over 50 years of age and able to give consent. Patients diagnosed with MCI or AD will be included in our study. Other more severe symptomatic patients will be eligible to enroll, as long as they have the ability to consent for their participation. Screening is essential and will be performed by our collaborator and neurologist of the study, Dr. Lawrence Honig, MD at the Taub Institute of Alzheimer's Disease and Aging at Columbia. After the initial screening we will acquire MRI scans as part of the study and finalize enrollment or exclusion of the patient. Inclusion criteria thus include: * Age greater than 50 years old. * Diagnosis of MCI or AD. All following criteria must be met: * MMSE score between 12 and 26. * Modified Hachinski Ischemia Scale (MHIS) score of \<= 4 * Short form Geriatric Depression Scale (GDS) score of \<= 6. * PET scan confirming amyloid plaque load using Amyvid (18F-Florbetapir). * PET scan confirming tau positivity in the frontal lobe using MK-6240 (F18-Florquinitau). * Ability to provide informed consent. Exclusion Criteria. Exclusion criteria include surgeries and other pathologies not associated with AD, as outlined in the following list: * Prior administration of any amyloid-reducing agent such as aducanumab or lecanemab. * Contraindication for MRI. * Contra-indication history or hypersensitivity to MRI contrast agents (e.g., Dotarem) or microbubbles (e.g., Definity, Lumason), including polyethylene glycol (PEG) allergy. * Prior brain surgery, including deep brain stimulation. * Metallic implants. * Abnormal coagulation profile (significant abnormality in PT, PTT, or platelets). * Anticoagulant therapy. * History of seizure disorder. * Brain atrophy to a degree that would interfere with ultrasound delivery. * Inability to comply with the procedures of the protocol, including follow-up scans. * Women with capacity to bear children or lactating. * Impaired renal function with estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73m2 provided by a standard blood test 2-4 weeks prior to the ultrasound treatment. * Active infection/inflammation. * Acute or chronic hemorrhages, i.e. \> 4 lobar microbleeds, or an area of siderosis or macrohemorrhages. * Tumors or space-occupying lesions of significance. * Any uncontrolled medical disorder that might interfere with the ability to safely perform the study.

Study sites (1)

NY